Recurrent stress urinary incontinence surgery in the United Kingdom: an analysis of the British Society of Urogynaecology database (2007-2015).

INTRODUCTION AND HYPOTHESIS: There is a lack of robust evidence guiding treatment options for recurrent stress urinary incontinence (SUI) and limited comparative outcome data. The aim of this study was to examine the pattern of surgery for recurrent SUI performed by gynaecologists in the UK and compare subjective success rates. METHODS: Retrospective review of the British Society of Urogynaecologists database for patients having repeat incontinence procedures (2007-2015) including the number of each procedure and outcome recorded by the International Consultation on Incontinence Urinary Incontinence Short Form (ICIQ-UI-SF) questionnaire. Procedures were compared by year and outcomes by operation. Categorical comparisons were performed using Chi-squared test and numerical comparisons using appropriate non-parametric tests. RESULTS: A total of 2,938 records were obtained (269 were excluded) and 2,164 women (88.8%) had undergone one previous procedure, most commonly retropubic midurethral sling (MUS; 28.6%). Pelvic floor exercises were offered to 76.2% women. Urodynamic investigation was carried out in 96.2% women: 76.5% had urodynamic stress incontinence. Repeat MUS was the most common procedure (77.3%), followed by bladder neck injections (BNI; 10.2%). Follow-up details were available for 66.1%. Outcome data were poorly reported. Median ICIQ-UI-SF score fell from 16 (0-21) to 0 (0-21) (p < 0.001), 81.6% felt "much better" or "very much better" on Patient Global Impression of Improvement (PGI-I), and 89.3% "cured" or "improved". MUS, colposuspension and fascial sling showed the best results with regard to the PGI-I score and "change in SUI" (p < 0.001). CONCLUSION: MUS and BNI were the most common repeat continence procedures. Follow-up data suggest that MUS, colposuspension and fascial sling are most effective.

Multivariate network meta-analysis incorporating class effects.

BACKGROUND: Network meta-analysis synthesises data from a number of clinical trials in order to assess the comparative efficacy of multiple healthcare interventions in similar patient populations. In situations where clinical trial data are heterogeneously reported i.e. data are missing for one or more outcomes of interest, synthesising such data can lead to disconnected networks of evidence, increased uncertainty, and potentially biased estimates which can have severe implications for decision-making. To overcome this issue, strength can be borrowed between outcomes of interest in multivariate network meta-analyses. Furthermore, in situations where there are relatively few trials informing each treatment comparison, there is a potential issue with the sparsity of data in the treatment networks, which can lead to substantial parameter uncertainty. A multivariate network meta-analysis approach can be further extended to borrow strength between interventions of the same class using hierarchical models. METHODS: We extend the trivariate network meta-analysis model to incorporate the exchangeability between treatment effects belonging to the same class of intervention to increase precision in treatment effect estimates. We further incorporate a missing data framework to estimate uncertainty in trials that did not report measures of variability in order to maximise the use of all available information for healthcare decision-making. The methods are applied to a motivating dataset in overactive bladder syndrome. The outcomes of interest were mean change from baseline in incontinence, voiding and urgency episodes. All models were fitted using Bayesian Markov Chain Monte Carlo (MCMC) methods in WinBUGS. RESULTS: All models (univariate, multivariate, and multivariate models incorporating class effects) produced similar point estimates for all treatment effects. Incorporating class effects in multivariate models often increased precision in treatment effect estimates. CONCLUSIONS: Multivariate network meta-analysis incorporating class effects allowed for the comparison of all interventions across all outcome measures to ameliorate the potential impact of outcome reporting bias, and further borrowed strength between interventions belonging to the same class of treatment to increase the precision in treatment effect estimates for healthcare policy and decision-making.

Risk factors for perineal trauma in the primiparous population during non-operative vaginal delivery.

INTRODUCTION AND HYPOTHESIS: Obstetric anal sphincter injuries (OASIS) are more common in the primiparous population, especially during operative vaginal delivery (OVD). It would therefore be interesting to establish what factors influence the risk of OASIS when adjusting for the risk bias of OVD. METHODS: Retrospective analysis of prospectively collected data from the maternity database at University of Southampton NHS Foundation Trust of primiparous women sustaining OASIS during a singleton, term, cephalic, non-operative vaginal delivery between 2004 and 2015. A control comparison was made of women with otherwise identical birthing conditions but resulting with intact perinea, delivering between 2014 and 2015. Univariate and multivariate logistic regression compared maternal, intrapartum and neonatal factors of those sustaining OASIS with those with an intact perineum. RESULTS: Seven hundred fifty-six women sustaining an OASI met the criteria, and comparisons were made with a control population of 212. Those sustaining an OASI were significantly older (p < 0.001), more likely to be Asian (4.6-fold, p < 0.001) and had heavier babies, with a 3.6-fold greater proportion over 4 kg (p = 0.001). They were more likely to have delivered post-term and had longer second stages of labour (both p < 0.001). Epidural anaesthesia was associated with a 67% reduction in OASIS. CONCLUSIONS: These findings support previous research regarding risk factors for OASIS. By controlling for bias of risk associated with operative vaginal delivery, this revealed a potential protective effect of the use of regional anaesthesia.

Maternal outcomes in subsequent delivery after previous obstetric anal sphincter injury (OASI): a multi-centre retrospective cohort study.

INTRODUCTION AND HYPOTHESIS: Women with a history of obstetric anal sphincter injury (OASI) are at increased risk of recurrence (rOASI) at subsequent delivery; however, evidence regarding the factors influencing this risk is limited. Furthermore, little is known about what factors influence the decision to alternatively deliver by elective caesarean section (ELLSCS). METHODS: Retrospective univariate and multivariate logistic regression analysis of prospectively collected data from four NHS electronic maternity databases including primiparous women sustaining OASIS during a singleton, term, cephalic, vaginal delivery between 2004 and 2015, who had a subsequent delivery. RESULTS: Two thousand two hundred seventy-two women met the criteria; 10.2% delivering vaginally had a repeat OASI and 59.4% had a second-degree tear. Women having an ELLSCS were more likely to be Caucasian, older, have previously had an operative vaginal delivery (OVD) and have a more severe degree of OASI. Positive predictors for rOASI were increased birth weight and maternal age at both index and subsequent deliveries, a more severe degree of initial OASI and Asian ethnicity. The overall mediolateral episiotomy (MLE) rate was 15.6%; 77.2% of those who had an episiotomy sustained no spontaneous perineal trauma. Only 4.4% of women with a rOASI had an MLE, whilst the MLE rate was 16.9% in those without a recurrence (p < 0.001). MLE decreased the risk of rOASI by 80%. Birth weight > 4 kg increased the risk 2.5 fold. CONCLUSIONS: Women with previous OASIS are at an increased risk of recurrence. A more liberal use of MLE during subsequent vaginal delivery could significantly reduce the risk of recurrence.

Validation of a water-load protocol to define the pattern of bladder sensation.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to confirm reliability of a water-load diuresis protocol and to assess the utility of bladder sensation curves. METHODS: For confirmation of fixed diuresis rate (phase 1), 12 volunteers consumed 250-300 ml of water every 15 min and recorded bladder sensation on a visual analogue scale (VAS) every 5 min to maximum sensation over two filling cycles: voids 1 and 2 (V1 and V2). The test was performed twice. For test-retest validation (phase 2), 24 participants underwent the same protocol drinking 300 ml of water every 15 min. Diuresis rates and voided volumes were compared between cycles and across tests. RESULTS: In phase 1, there was no difference in median void volume (V1 735 ml, V2 678 ml p = 0.433) or median diuresis rates (V2 12.1 ml/min, V3 14.4 ml/min p = 0.136) between cycles. When comparing those who drank 250-300 ml/15 min, there was less variability in those drinking 300-ml aliquots, so this was standardised for later experiments; 95% upper confidence limit of variability of the diuresis rate was calculated as 4.5 ml/min. Any test with a greater difference was rejected as invalid. In phase 2, only 16 participants were analysed. There was no difference in median void volumes between tests [V1 763 ml and 820 ml (p = 0.109) and V2 788 ml and 796 ml (p = 0.266)] or in diuresis rates between test 1 (12.33 ml/min) and 2 (14.40 ml/min) (p = 0.056). Median area under the curve was similar between test 1 404.96 and test 2 418.63. CONCLUSIONS: This refined protocol reliably produced stable diuresis with a water load of 300 ml/15 min, excluding those with a difference in diuresis rate > 4.5 ml/min.

Methods of assessing and recording bladder sensation: a review of the literature.

INTRODUCTION AND HYPOTHESIS: The objective was to review different methods that have been used to assess bladder sensation and to provide an overview of the accuracy and objectivity of the measurement of the subjective perception of the bladder. METHODS: The MEDLINE and PubMed databases were searched to identify articles. References from those articles were also searched. Terms used for the search were: urinary bladder, sensation, cystometry, urodynamics, urinary incontinence and focus group. Eight hundred and fifty abstracts were identified from databases, and 12 from other sources. Twenty-two duplicate articles were removed. Irrelevant articles were excluded after reading their titles. Fifty-four articles were eligible, but 17 were excluded after reading the full text, leaving 37 articles where assessment of bladder sensation was the main aim. RESULTS: Six different methods of measuring bladder sensation have been described in the literature. Although the most frequently used was cystometry, this is an invasive tool and does not reproduce bladder behaviour during daily life because it records bladder sensation as episodic events. The visual analogue scale using a forced diuresis protocol seemed to be an excellent tool. It was non-invasive and evaluated bladder sensation continuously, from an empty to a full bladder. CONCLUSIONS: In some of the studies, the samples were too small to draw any significant conclusions. There were also conflicting data on which tool was the most accurate, especially as each method of evaluating bladder sensation may influence the way it is described by participants.

Risk factors for obstetric anal sphincter injuries at vaginal birth after caesarean: a retrospective cohort study.

INTRODUCTION AND HYPOTHESIS: Vaginal birth after caesarean (VBAC) is associated with an increased risk of obstetric anal sphincter injuries (OASIS). However, specific factors that influence the risk of OASIS at VBAC have not been studied, particularly whether there are specific baseline characteristics of the first delivery which affect the subsequent perineal outcomes. METHODS: Retrospective analysis of prospectively collected data from University of Southampton NHS Foundation Trusts' maternity database. This included secundiparous women with a previous caesarean delivery (CS) who achieved a singleton, term, cephalic vaginal delivery from 2004 to 2014. Univariate analysis compared maternal, intrapartum and neonatal factors of those who suffered OASIS at VBAC with those who did not. A binary logistic regression model calculated the adjusted, independent odds ratio (OR) of OASIS. RESULTS: A total of 1375 women met the inclusion criteria. The OASIS rate was 8.1%, a 1.4-fold increase compared with primiparous women [difference 2.4% (95% CI 1.1, 3.6)]. Those sustaining OASIS at VBAC were older (p = 0.011) and had infants of greater birth weight at initial caesarean (p < 0.001) and VBAC (p = 0.04). Analysis of odds ratios revealed that mediolateral episiotomy (MLE) at VBAC halved the risk of OASIS [37.5% VBAC with OASIS vs. 52.2% VBAC without OASIS (OR 0.51, 95% CI 0.32-0.81)], whereas an urgent CS at initial delivery doubled the risk [52.3% VBAC with OASIS vs. 34.9% VBAC without OASIS (OR 2.05, 95% CI 1.31-3.21)]. CONCLUSIONS: Advanced maternal age, increased infant birth weight and an urgent category of initial CS increase the risk of OASIS at VBAC, whereas MLE is protective.

Interventions for treating recurrent stress urinary incontinence after failed minimally invasive synthetic midurethral tape surgery in women.

BACKGROUND: Surgery is a common treatment modality for stress urinary incontinence (SUI), usually offered to women for whom conservative treatments have failed. Midurethral tapes have superseded colposuspension because cure rates are comparable and recovery time is reduced. However, some women will not be cured after midurethral tape surgery. Currently, there is no consensus on how to manage the condition in these women.This is an update of a Cochrane Review first published in 2013. OBJECTIVES: To assess the effects of interventions for treating recurrent stress urinary incontinence after failed minimally invasive synthetic midurethral tape surgery in women; and to summarise the principal findings of economic evaluations of these interventions. SEARCH METHODS: We searched the Cochrane Incontinence Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings (searched 9 November 2018). We also searched the reference lists of relevant articles. SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials in women who had recurrent stress urinary incontinence after previous minimally invasive midurethral tape surgery. We included conservative, pharmacological and surgical treatments. DATA COLLECTION AND ANALYSIS: Two review authors checked the abstracts of identified studies to confirm their eligibility. We obtained full-text reports of relevant studies and contacted study authors directly for additional information where necessary. We extracted outcome data onto a standard proforma and processed them according to the guidance in the Cochrane Handbook for Systematic Reviews of Interventions. MAIN RESULTS: We included one study in this review. This study was later reported in an originally unplanned secondary analysis of 46 women who underwent transobturator tape for recurrent SUI after one or more previous failed operations. We were unable to use the data, as they were not presented according to the nature of the first operation.We excluded 12 studies, five because they were not randomised controlled trials (RCTs) and four because previous incontinence surgery was not performed using midurethral tape. We considered a further three to be ineligible because neither the trial report nor personal communication with the trialists could confirm whether any of the participants had previously undergone surgery with tape.We had also planned to develop a brief economic commentary summarising the principal findings of relevant economic evaluations but supplementary systematic searches did not identify any such studies. AUTHORS' CONCLUSIONS: There were insufficient data to assess the effects of any of the different management strategies for recurrent or persistent stress incontinence after failed midurethral tape surgery. No published papers have reported exclusively on women whose first operation was a midurethral tape. Evidence from further RCTs and economic evaluations is required to address uncertainties about the effects and costs of these treatments.

Evaluation of the IncoStress device for urinary incontinence: a feasibility study and pilot randomised controlled trial.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to assess the feasibility of recruitment to and outcomes from a pilot randomised study of the IncoStress device as an adjunct to conservative treatment for urinary incontinence. METHODS: Women with urinary incontinence were randomised on a 2:1 basis to usual care (control) or usual care plus use of the IncoStress device (intervention). Process outcomes (retention and compliance) were recorded plus symptom outcomes (IQOL and ICIQ-FLUTS questionnaires). A sample of participants took part in an interview to understand the frequency of use of the device and satisfaction. RESULTS: Eighty women (51 intervention, 29 control) were recruited. Follow-up responses were obtained from 34 intervention group (66.7%) and 17 (58.6%) control patients. Women used the device for a median 3 days a week (0-7), 18 out of 34 (53%) found it easy to use and 21 (61.8%) were satisfied with the device. Median IQOL score in the intervention group improved from a baseline of 42.4 (0-94) to 68.2 (5-98) at follow-up and in the control group from 45.5 (0-88) to 53.0 (0-94). Median ICIQ-FLUTS score in the intervention group improved from 14.5 (6-35) to 12.5 (4-26) and in the control group from 15.0 (5-35) to 14.0 (6-38). CONCLUSIONS: Recruitment and randomisation were feasible and robust. This study demonstrates that a large-scale RCT is feasible and the IncoStress has potential value.

Acceptability and utilisation of patient-initiated follow-up for endometrial cancer amongst women from diverse ethnic and social backgrounds: A mixed methods study.

INTRODUCTION: A shift in focus towards risk stratification and survivorship in early stage endometrial cancer (EC) has led to the replacement of hospital follow-up (HFU) with patient-initiated follow-up (PIFU) schemes. METHODS: A mixed methods study was undertaken prospectively to investigate utility and patient satisfaction with a newly introduced PIFU scheme. RESULTS: Two hundred and twenty-eight women were enrolled onto PIFU in the first 18 months, median age 65 years (range 42-90 years). Twenty-four (10.5%) women were non-British White ethnicity. Forty-five women contacted the Clinical Nurse Specialist (CNS) at least once (19.7%), the primary reason being vaginal bleeding/discharge (42%). Contact was greater in first six months on the scheme compared to the second 6 months, and women who made contact were significantly younger than those who did not (57 years vs. 65 years, p < 0.001). CONCLUSIONS: PIFU appears to be well received by the majority of women. Although many of the CNS contacts were due to physical symptoms, a number were for psychological support or reassurance. Younger women had greater CNS contact indicating that they may benefit from a greater level support. Patient feedback of the PIFU scheme was positive, with many women reporting that it enabled them to have more control over their own health.

Surgery for recurrent stress urinary incontinence: the views of surgeons and women.

INTRODUCTION AND HYPOTHESIS: The objectives were to explore the views of women with recurrent stress incontinence (SUI) with regard to treatment preferences and the acceptability of randomisation to a future trial, and to survey the views of UK specialists on treatment preferences and equipoise regarding different treatment alternatives. METHODS: An online survey of the British Society of Urogynaecology (BSUG) and British Society of Urological Surgeons (BAUS) was carried out. Qualitative semi-structured interviews with a purposive sample of surgeons and women suffering from recurrent SUI from three UK centres. RESULTS: Two hundred fifty-six survey replies were received (176 gynaecology; 80 urology). Comparing the treatments offered, urogynaecologists were more likely to offer pelvic floor exercises (p < 0.05), and repeat midurethral tape (MUT) (p < 0.001). From the Surgical Equipoise Scale (SES) responses, "no preference" was rarely the commonest response. Marked differences for several options existed; midurethral tape dominated responses whenever it appeared. Twenty-one clinicians were interviewed. Treatment preferences were complex, influenced by a range of factors (reason for failure, patient comorbidity, investigations, personal experience, training). A future trial was regarded as important. Eleven women were interviewed. Most had considered more than one option, but felt that decision-making was more a process of elimination rather than a positive process. Randomisation to a study was regarded as unacceptable by most. CONCLUSIONS: No consensus exists among surgeons about preferred treatment options for recurrent SUI, and personal experience and training dominate decision-making. For patients, choices were usually based on an elimination of options, including that of a repeat failed procedure. This contrasts with surgeons, who mostly preferred a repeat MUT above other options. Any future comparative study will be challenging.

Long-term Rate of Mesh Sling Removal Following Midurethral Mesh Sling Insertion Among Women With Stress Urinary Incontinence.

Importance: There is concern about outcomes of midurethral mesh sling insertion for women with stress urinary incontinence. However, there is little evidence on long-term outcomes. Objective: To examine long-term mesh removal and reoperation rates in women who had a midurethral mesh sling insertion for stress urinary incontinence. Design, Setting, and Participants: This population-based retrospective cohort study included 95 057 women aged 18 years or older who had a first-ever midurethral mesh sling insertion for stress urinary incontinence in the National Health Service hospitals in England between April 1, 2006, and December 31, 2015. Women were followed up until April 1, 2016. Exposures: Patient and hospital factors and retropubic or transobturator mesh sling insertions. Main Outcomes and Measures: The primary outcome was the risk of midurethral mesh sling removal (partial or total) and secondary outcomes were reoperation for stress urinary incontinence and any reoperation including mesh removal, calculated with death as competing risk. A multivariable Fine-Gray model was used to calculate subdistribution hazard ratios as estimates of relative risk. Results: The study population consisted of 95 057 women (median age, 51 years; interquartile range, 44-61 years) with first midurethral mesh sling insertion, including 60 194 with retropubic insertion and 34 863 with transobturator insertion. The median follow-up time was 5.5 years (interquartile range, 3.2-7.5 years). The rate of midurethral mesh sling removal was 1.4% (95% CI, 1.3%-1.4%) at 1 year, 2.7% (95% CI, 2.6%-2.8%) at 5 years, and 3.3% (95% CI, 3.2%-3.4%) at 9 years. Risk of removal declined with age. The 9-year removal risk after transobturator insertion (2.7% [95% CI, 2.4%-2.9%]) was lower than the risk after retropubic insertion (3.6% [95% CI, 3.5%-3.8%]; subdistribution hazard ratio, 0.72 [95% CI, 0.62-0.84]). The rate of reoperation for stress urinary incontinence was 1.3% (95% CI, 1.3%-1.4%) at 1 year, 3.5% (95% CI, 3.4%-3.6%) at 5 years, and 4.5% (95% CI, 4.3%-4.7%) at 9 years. The rate of any reoperation, including mesh removal, was 2.6% (95% CI, 2.5%-2.7%) at 1 year, 5.5% (95% CI, 5.4%-5.7%) at 5 years, and 6.9% (95% CI, 6.7%-7.1%) at 9 years. Conclusions and Relevance: Among women undergoing midurethral mesh sling insertion, the rate of mesh sling removal at 9 years was estimated as 3.3%. These findings may guide women and their surgeons when making decisions about surgical treatment of stress urinary incontinence.

Patient factors associated with onabotulinum toxin A treatment outcome in women with detrusor overactivity.

OBJECTIVE: To evaluate potential predictors of non-response to treatment with 200U onabotulinum toxin A (onaBoNTA) in women with refractory detrusor overactivity (DO). SUBJECTS AND METHODS: A secondary analysis of a randomized trial of 200U onaBoNTA versus placebo in women with refractory DO analyzed baseline and 6 week follow-up data. Univariate and multivariate logistic regression were used to assess demographic factors and baseline clinical parameters on non-response to treatment defined as 20% or less improvement in urinary urgency and leakage episodes, 10% or less in voiding frequency, not achieving continence, and "no change" or worse on PGI-I score at 6 weeks. RESULTS: One Hundred and twenty-two women were included. Twenty-nine (23.8%), 24 (19.7%), and 19 (15.6%) were non-responders to treatment for urgency, voiding, and leakage episodes, respectively. Fifty-nine (48.4%) failed to achieve continence, and 28 (23%) were non-responders on the PGI-I scale. Smoking status (OR: 2.89 95%CI 1.08, 7.73, P = 0.034) predicted non-response in urgency episodes, and higher baseline leakage episodes (OR: 1.17 95%CI 1.04, 1.31, P = 0.007) predicted non-response in achieving continence. Increasing age (OR 1.04, 95%CI 1.0, 1.09, P = 0.063) and body mass index (BMI) (OR 1.07, 95%CI 1.0, 1.16, P = 0.065) showed marginal associations with non-response on the PGI-I scale. CONCLUSION: onaBoNTA is an effective treatment for refractory DO, but some fail to respond. For identification of women at risk, our data indicate smokers should be advised of a lesser chance of successful treatment. Older women, those with high BMI and with more severe leakage also have a higher risk of failure. Neurourol. Urodynam. 36:426-431, 2017. © 2016 Wiley Periodicals, Inc.

Comparison of the effectiveness of repeated injections of onabotulinum toxin A for refractory idiopathic detrusor overactivity: analysis of an open label extension of a randomized trial (the RELAX study).

AIMS: To assess effects of repeat treatment with onabotulinumtoxin A (onaBoNT-A) in women with refractory idiopathic detrusor overactivity (DO). METHODS: Analysis of an open-label extension study of a large randomized placebo controlled trial of onaBoNT-A. Participants had been randomized to receive 200 IU onaBoNTA or placebo and were offered up to two further onaBoNTA injections over a 5-year period. For this analysis, the primary outcome was duration of treatment effect by patient-reported symptom return. Weibull proportional hazards regression models were fitted in a Bayesian framework to estimate missing times. Multivariable hazard regression analysis (hazard ratio, 95% credible intervals (HR, 95% CrI) compared repeated injections adjusting for differences in baseline symptom severity. Secondary outcomes included inter-injection interval, incontinence, urgency, and voiding episodes 6 weeks after injection. RESULTS: Four hundred and forty-two active injections were administered: 228 patients had one, 155 had two, and 59 had three injections. Time to symptom return for injection number 1 and 2 was 84 (95%CI: 63, 112) and 180 (95%CI: 135, 223) days, respectively. Median inter-injection intervals for receiving second and third injection were 266 days (range: 130, 1400) and 372 days (range: 134, 1283). No statistically significant differences in symptom outcomes or time to symptom return (HR 0.88, 95% CrI 0.37, 2.07 for injection 2, HR 0.33, 95% CrI 0.09, 1.03 for injection 3) were observed. CONCLUSIONS: Repeated onaBoNT-A injections have consistent efficacy and duration of action. There appears to be long-term placebo effects in both groups of randomized patients, with implications for open-label extension studies.

Cannabinoid receptor expression in the bladder is altered in detrusor overactivity.

INTRODUCTION: Immunohistochemical (IHC) evidence shows that cannabinoid receptors (CB) are expressed in human bladders and cannabinoid agonists are known to inhibit detrusor contractility. However, the mechanism for this inhibition remains unknown. In addition, the role of CB in detrusor overactivity (DO) is under-investigated. The aim of this study was to compare CB expression in normal and DO human bladders and to further characterise these receptors. METHODS: Polymer chain reaction (PCR) was used to detect differences in CB transcripts in bladder samples. Differences in CB protein expression was assessed by IHC. Immunofluorescence (IF) was used to evaluate co-localisation of CB with nerve fibres. Receptor density and binding affinity were measured using the cannabinoid radioligand [(3)H]-CP-55,940. RESULTS: There were higher levels of CB1 transcripts in the urothelium of patients with DO and lower levels in the detrusor, compared with normal bladders. Radioligand binding revealed CB density of 421 ± 104 fmol/mg protein in normal human bladders. IHC confirmed these findings at the protein level. IF staining demonstrated co-localisation of CB1 with choline acetyltransferase-(ChAT)-positive nerves in the detrusor and co-localisation with PGP9.5 in both urothelium and detrusor. CB2 was co-localised with both ChAT and PGP9.5 in the urothelium and the detrusor. CONCLUSIONS: Cannabinoid receptor expression is reduced in the detrusor of patients with DO, which may play a role in the pathophysiology of the disease. Co-localisation of CB receptors with cholinergic nerves may suggest that CB1, being localised on pre- and postsynaptic terminals, could influence neurotransmitter release. Our findings suggest the potential role of cannabinoid agonists in overactive bladder pharmacotherapy.

Early postoperative voiding dysfunction after insertion of retropubic midurethral tape.

INTRODUCTION AND HYPOTHESIS: A significant proportion of patients develop voiding dysfunction after midurethral tape (MUT) insertion, which reduces patient satisfaction. The study's purpose was to identify predictive factors of voiding dysfunction after a retropubic MUT procedure. METHODS: This was a retrospective study of 100 patients who underwent only a retropubic MUT procedure between January 2010 and December 2011. Early voiding dysfunction was defined when patients required a Foley catheter within 48 h. Data including demographic information, urogenital symptoms, previous surgery, preoperative uroflowmetry and urodynamic parameters were analysed using SPSS v22. Univariate analysis of all demographic variables was performed; those significant at 10 % were entered into a multivariate logistic regression. RESULTS: Fourteen patients required Foley catheter insertion, with a median age of 58 years (26-83 years), median BMI 28 kg/m(2) (20-48 kg/m2), and median parity 2 (0-4). Univariate analysis revealed peak flow rate <15 ml/s (OR 3.79; 1.07, 13.4; p = 0.046), bladder capacity (p = 0.044), stress incontinence versus mixed or urge incontinence (p = 0.064) and previous surgery (OR 4.39; 1.34, 14.41; p = 0.015) to be associated with voiding dysfunction. Multivariate analysis showed only previous pelvic floor surgery to be independently associated (OR 3.76; 1.14, 12.23, p = 0.029). CONCLUSIONS: Only previous pelvic-floor surgery was found to be a strong predictive factor of voiding dysfunction. The rate of voiding dysfunction was similar to those of published data. Previous studies revealed different predictive factors. A larger cohort is needed to provide a definite answer. Those with previous surgery appear to be those most at risk and pre-surgical counselling for these women could be suggested.

Effects of cannabinoid receptor activation by CP55,940 on normal bladder function and irritation-induced bladder overactivity in non-awake anaesthetised rats.

INTRODUCTION AND HYPOTHESIS: This study was designed to evaluate the effects of CP55,940 on normal bladder function in vivo and examine whether it suppresses urinary frequency induced by nociceptive stimuli in the bladder. Cannabinoid receptor (CBR) activity may be involved in the regulation of bladder function. However, the role of CBR subtypes in micturition has yet to be established. CP55,940 is a synthetic analogue of tetrahydrocannabidiol, which is a psychoactive ingredient of the Cannabis plant. METHODS: Cystometry under urethane anaesthesia was performed to evaluate the effect of intravesical delivery of CP55,940 with or without administration of CB1 antagonist AM251 or CB2 antagonist AM630 on bladder function in female rats. The effects of CP55,940 were also examined in rats with urinary irritation induced by intravesical infusion of acetic acid. RESULTS: Infusion of CP55,940 significantly (p < 0.05) increased micturition interval (MI) and bladder capacity (BC) by 52 % and decreased maximal voiding pressure (MP) by 25 %. Pretreatment with AM251 or AM630 before CP55,940 administration prevented CP55,940-induced increases in MI, BC and reduced MP. Acetic acid induced urinary frequency as evidenced by a reduction in MI and was suppressed by CP55,940. CONCLUSIONS: CP55,940 decreases bladder activity and urinary frequency induced by nociceptive stimuli, probably by suppression of bladder afferent activity. Effects of CP55,940 were abolished by both CBR antagonists. This data implicates a role for the endocannabinoid system in bladder mechanoafferent function in rats. In addition, our results show that CP55,940 reverses urinary frequency exemplified in an overactive bladder model, suggesting it could be an effective treatment for patients with lower urinary tract symptoms.

Trial participation as avoidance strategy: a qualitative study.

BACKGROUND: Trial participation decisions are often influenced by expectations of potential benefit. Attention has focused on trial participation as a means of securing something seen as desirable, such as experimental treatment. In contrast, we consider a case in which one trial arm involved receiving less than usual care. We explore how this influenced participants' decisions to participate. METHODS: Semi-structured interviews with 29 women participating in a pilot trial comparing invasive urodynamic testing (typically normal care) to basic clinical assessment with non-invasive tests, prior to surgical treatment for stress urinary incontinence. Analysis was based on the constant comparative method. RESULTS: Invasive tests were something many were aware of and worried about. Participants understood that trial participation meant they might avoid having these tests, and for about one-third, this was the primary factor motivating participation. A further third mentioned they were not looking forward to tests (if allocated to them) or were lucky to have missed them (if allocated to basic clinical assessment). None of the women appeared to have discussed their desire to avoid having invasive tests with their clinicians. CONCLUSIONS: In contrast to cases in which trial participation is motivated by the wish to secure an intervention not otherwise available, this study reports the opposite - trial participation as an opportunity to avoid having something regarded as undesirable. The option to decline a particular intervention should always be available, and care must be taken to ensure that potential participants are aware that trial participation is not the only possible means of avoidance.

Network meta-analysis: development of a three-level hierarchical modeling approach incorporating dose-related constraints.

BACKGROUND: Network meta-analysis (NMA) is commonly used in evidence synthesis; however, in situations in which there are a large number of treatment options, which may be subdivided into classes, and relatively few trials, NMAs produce considerable uncertainty in the estimated treatment effects, and consequently, identification of the most beneficial intervention remains inconclusive. OBJECTIVE: To develop and demonstrate the use of evidence synthesis methods to evaluate extensive treatment networks with a limited number of trials, making use of classes. METHODS: Using Bayesian Markov chain Monte Carlo methods, we build on the existing work of a random effects NMA to develop a three-level hierarchical NMA model that accounts for the exchangeability between treatments within the same class as well as for the residual between-study heterogeneity. We demonstrate the application of these methods to a continuous and binary outcome, using a motivating example of overactive bladder. We illustrate methods for incorporating ordering constraints in increasing doses, model selection, and assessing inconsistency between the direct and indirect evidence. RESULTS: The methods were applied to a data set obtained from a systematic literature review of trials for overactive bladder, evaluating the mean reduction in incontinence episodes from baseline and the number of patients reporting one or more adverse events. The data set involved 72 trials comparing 34 interventions that were categorized into nine classes of interventions, including placebo. CONCLUSIONS: Bayesian three-level hierarchical NMAs have the potential to increase the precision in the effect estimates while maintaining the interpretability of the individual interventions for decision making.

Women's expectations of prolapse surgery: a retrospective qualitative study.

AIMS: To explore the expectations of prolapse surgery held by women before that surgery and to examine reasons why such expectations were met, or not met. METHODS: Qualitative study using one-to-one interviews with women who had undergone prolapse surgery in a large UK teaching hospital. Interviews were conducted by a third party, trained interviewer using a piloted interview guide, but women were encouraged to speak freely. Transcripts were analyzed based on the constant comparative method and interviews continued until no new themes emerged. RESULTS: Fifty-two women were contacted; 32 took part. Twenty-eight women's interviews were used for analysis, after pilot interviews with four women. Median age was 58 (32-86), 19 were Caucasian, nine of South Indian ethnicity. Anticipated benefits of surgery included global themes of cure without specific definitions, focusing on physical symptoms. A few women anticipated psychological benefit. Most women had expectations of a permanent cure. After surgery, most women considered their surgery a success, for physical symptom improvement. Some women had modified their prior expectations (downwards) and success was interpreted in this light. Provision of information about recovery and symptom resolution was felt to be inadequate by the majority. CONCLUSIONS: In this study, resolution of physical symptoms was the prevalent expectation, along with restoration of "normality." Normality was often redefined during recovery, indicating the complexity of assessing fulfillment of expectations, and that specific goal-setting may be inadequate. A chronic illness framework for prolapse may be helpful. Information exchange, especially in the post-operative period can be improved.